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Daniel D. Cavalcanti, Mark C. Preul, M. Yashar S. Kalani and Robert F. Spetzler

OBJECT

The aim of this study was to enhance the planning and use of microsurgical resection techniques for intrinsic brainstem lesions by better defining anatomical safe entry zones.

METHODS

Five cadaveric heads were dissected using 10 surgical approaches per head. Stepwise dissections focused on the actual areas of brainstem surface that were exposed through each approach and an analysis of the structures found, as well as which safe entry zones were accessible via each of the 10 surgical windows.

RESULTS

Thirteen safe entry zones have been reported and validated for approaching lesions in the brainstem, including the anterior mesencephalic zone, lateral mesencephalic sulcus, intercollicular region, peritrigeminal zone, supratrigeminal zone, lateral pontine zone, supracollicularzone, infracollicularzone, median sulcus of the fourth ventricle, anterolateral and posterior median sulci of the medulla, olivary zone, and lateral medullary zone. A discussion of the approaches, anatomy, and limitations of these entry zones is included.

CONCLUSIONS

A detailed understanding of the anatomy, area of exposure, and safe entry zones for each major approach allows for improved surgical planning and dissemination of the techniques required to successfully resect intrinsic brainstem lesions.

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M. Yashar S. Kalani, Kaan Yagmurlu, Nikolay L. Martirosyan, Daniel D. Cavalcanti and Robert F. Spetzler

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Nikolay L. Martirosyan, Jeanne S. Feuerstein, Nicholas Theodore, Daniel D. Cavalcanti, Robert F. Spetzler and Mark C. Preul

The authors present a review of spinal cord blood supply, discussing the anatomy of the vascular system and physiological aspects of blood flow regulation in normal and injured spinal cords. Unique anatomical functional properties of vessels and blood supply determine the susceptibility of the spinal cord to damage, especially ischemia. Spinal cord injury (SCI), for example, complicating thoracoabdominal aortic aneurysm repair is associated with ischemic trauma. The rate of this devastating complication has been decreased significantly by instituting physiological methods of protection. Traumatic SCI causes complex changes in spinal cord blood flow, which are closely related to the severity of injury. Manipulating physiological parameters such as mean arterial blood pressure and intrathecal pressure may be beneficial for patients with an SCI. Studying the physiopathological processes of the spinal cord under vascular compromise remains challenging because of its central role in almost all of the body's hemodynamic and neurofunctional processes.

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Editorial

Cavernous malformations

Issam A. Awad

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Daniel D. Cavalcanti, M. Yashar S. Kalani, Nikolay L. Martirosyan, Justin Eales, Robert F. Spetzler and Mark C. Preul

Over the past half century molecular biology has led to great advances in our understanding of angio- and vasculogenesis and in the treatment of malformations resulting from these processes gone awry. Given their sporadic and familial distribution, their developmental and pathological link to capillary telangiectasias, and their observed chromosomal abnormalities, cerebral cavernous malformations (CCMs) are regarded as akin to cancerous growths. Although the exact pathological mechanisms involved in the formation of CCMs are still not well understood, the identification of 3 genetic loci has begun to shed light on key developmental pathways involved in CCM pathogenesis. Cavernous malformations can occur sporadically or in an autosomal dominant fashion. Familial forms of CCMs have been attributed to mutations at 3 different loci implicated in regulating important processes such as proliferation and differentiation of angiogenic precursors and members of the apoptotic machinery. These processes are important for the generation, maintenance, and pruning of every vessel in the body. In this review the authors highlight the latest discoveries pertaining to the molecular genetics of CCMs, highlighting potential new therapeutic targets for the treatment of these lesions.

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Daniel D. Cavalcanti, William Feindel, James T. Goodrich, T. Forcht Dagi, Charles J. Prestigiacomo and Mark C. Preul

In the 15th century, brain illustration began to change from a schematic system that involved scant objective rendering of the brain, to accurate depictions based on anatomical dissections that demanded significant artistic talent. Notable examples of this innovation are the drawings of Leonardo da Vinci (1498–1504), Andreas Vesalius' association with the bottega of Titian to produce the drawings of Vesalius' De humani corporis fabrica (1543), and Christopher Wren's illustrations for Thomas Willis' Cerebri Anatome (1664). These works appeared during the Renaissance and Age of Enlightenment, when advances in brain imaging, or really brain rendering, reflected not only the abilities and dedications of the artists, but also the influences of important cultural and scientific factors. Anatomy and human dissection became popular social phenomena as well as scholarly pursuits, linked with the world of the fine arts. The working philosophy of these artists involved active participation in both anatomical study and illustration, and the belief that their discoveries of the natural world could best be communicated by rendering them in objective form (that is, with realistic perspective). From their studies emerged the beginning of contemporary brain imaging. In this article, the authors examine how the brain began to be imaged in realism within a cultural and scientific milieu that witnessed the emergence of anatomical dissection, the geometry of linear perspective, and the closer confluence of art and science.

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Ulises García-González, Daniel D. Cavalcanti, Abhishek Agrawal, L. Fernando Gonzalez, Robert C. Wallace, Robert F. Spetzler and Mark C. Preul

Object

There are few systematic investigations of the dissected surgical anatomy of the diploic venous system (DVS) in the neuroanatomical literature. The authors describe the DVS relative to different common neurosurgical approaches. Knowledge of this system can help avoid potential sources of unacceptable bleeding and may impact healing of the cranium.

Methods

Using a high-speed drill with a 2-mm bit, the authors removed the outer layer of the compact bone in the skull to expose the DVS in 12 formalin-fixed cadaver heads. Pterional, supraorbital, and modified orbitozygomatic craniotomies were performed to delineate the relationship of the DVS.

Results

The draining point of the frontal diploic vein (FDV) was located near the supraorbital notch. The draining point of the anterior temporal diploic vein (ATDV) was located in all pterional areas; the draining point of the posterior temporal diploic vein (PTDV) was located in all asterional areas. The PTDV was the dominant diploic vessel in all sides. The FDV and ATDV could be damaged during supraorbital, modified orbitozygomatic, and pterional craniotomies. The anterior DVS connected with the sphenoparietal and superior sagittal sinus (SSS). The posterior DVS connected with the transverse and sigmoid sinuses and was the dominant diploic vessel in all 24 sides. Of all the major diploic vessels, the location and pattern of distribution of the FDV were the most constant. The parietal bone contained the most diploic vessels. No diploic veins were found in the area delimited by the temporal squama.

Conclusions

The pterional, orbitozygomatic, and supraorbital approaches place the FDV and ATDV at risk. The major anterior diploic system connects the SSS with the sphenoparietal sinus. The posterior diploic system connects the SSS with the transverse and sigmoid sinuses.

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Nikolay L. Martirosyan, Daniel D. Cavalcanti, Jennifer M. Eschbacher, Peter M. Delaney, Adrienne C. Scheck, Mohammed G. Abdelwahab, Peter Nakaji, Robert F. Spetzler and Mark C. Preul

Object

Infiltrative tumor resection is based on regional (macroscopic) imaging identification of tumorous tissue and the attempt to delineate invasive tumor margins in macroscopically normal-appearing tissue, while preserving normal brain tissue. The authors tested miniaturized confocal fiberoptic endomicroscopy by using a near-infrared (NIR) imaging system with indocyanine green (ICG) as an in vivo tool to identify infiltrating glioblastoma cells and tumor margins.

Methods

Thirty mice underwent craniectomy and imaging in vivo 14 days after implantation with GL261-luc cells. A 0.4 mg/kg injection of ICG was administered intravenously. The NIR images of normal brain, obvious tumor, and peritumoral zones were collected using the handheld confocal endomicroscope probe. Histological samples were acquired from matching imaged areas for correlation of tissue images.

Results

In vivo NIR wavelength confocal endomicroscopy with ICG detects fluorescence of tumor cells. The NIR and ICG macroscopic imaging performed using a surgical microscope correlated generally to tumor and peritumor regions, but NIR confocal endomicroscopy performed using ICG revealed individual tumor cells and satellites within peritumoral tissue; a definitive tumor border; and striking fluorescent microvascular, cellular, and subcellular structures (for example, mitoses, nuclei) in various tumor regions correlating with standard clinical histological features and known tissue architecture.

Conclusions

Macroscopic fluorescence was effective for gross tumor detection, but NIR confocal endomicroscopy performed using ICG enhanced sensitivity of tumor detection, providing real-time true microscopic histological information precisely related to the site of imaging. This first-time use of such NIR technology to detect cancer suggests that combined macroscopic and microscopic in vivo ICG imaging could allow interactive identification of microscopic tumor cell infiltration into the brain, substantially improving intraoperative decisions.

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Daniel D. Cavalcanti, Nikolay L. Martirosyan, Ketan Verma, Sam Safavi-Abbasi, Randall W. Porter, Nicholas Theodore, Volker K. H. Sonntag, Curtis A. Dickman and Robert F. Spetzler

Object

Schwannomas occupying the craniocervical junction (CCJ) are rare and usually originate from the jugular foramen, hypoglossal nerves, and C-1 and C-2 nerves. Although they may have different origins, they may share the same symptoms, surgical approaches, and complications. An extension of these lesions along the posterior fossa cisterns, foramina, and spinal canal—usually involving various cranial nerves (CNs) and the vertebral and cerebellar arteries—poses a surgical challenge. The primary goals of both surgical and radiosurgical management of schwannomas in the CCJ are the preservation and restoration of function of the lower CNs, and of hearing and facial nerve function. The origins of schwannomas in the CCJ and their clinical presentation, surgical management, adjuvant stereotactic radiosurgery, and outcomes in 36 patients treated at Barrow Neurological Institute (BNI) are presented.

Methods

Between 1989 and 2009, 36 patients (mean age 43.6 years, range 17–68 years) with craniocervical schwannomas underwent surgical resection at BNI. The records were reviewed retrospectively regarding clinical presentation, radiographic assessment, surgical approaches, adjuvant therapies, and follow-up outcomes.

Results

Headache or neck pain was present in 72.2% of patients. Cranial nerve impairments, mainly involving the vagus nerve, were present in 14 patients (38.9%). Motor deficits were found in 27.8% of the patients. Sixteen tumors were intra- and extradural, 15 were intradural, and 5 were extradural. Gross-total resection was achieved in 25 patients (69.4%). Adjunctive radiosurgery was used in the management of residual tumor in 8 patients; tumor control was ultimately obtained in all cases.

Conclusions

Surgical removal, which is the treatment of choice, is curative when schwannomas in the CCJ are excised completely. The far-lateral approach and its variations are our preferred approaches for managing these lesions. Most common complications involve deficits of the lower CNs, and their early recognition and rehabilitation are needed. Stereotactic radiosurgery, an important tool for the management of these tumors as adjuvant therapy, can help decrease morbidity rates.

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Nikolay L. Martirosyan, Joseph Georges, Jennifer M. Eschbacher, Daniel D. Cavalcanti, Ali M. Elhadi, Mohammed G. Abdelwahab, Adrienne C. Scheck, Peter Nakaji, Robert F. Spetzler and Mark C. Preul

Object

The authors sought to assess the feasibility of a handheld visible-wavelength confocal endomicroscope imaging system (Optiscan 5.1, Optiscan Pty., Ltd.) using a variety of rapid-acting fluorophores to provide histological information on gliomas, tumor margins, and normal brain in animal models.

Methods

Mice (n = 25) implanted with GL261 cells were used to image fluorescein sodium (FNa), 5-aminolevulinic acid (5-ALA), acridine orange (AO), acriflavine (AF), and cresyl violet (CV). A U251 glioma xenograft model in rats (n = 5) was used to image sulforhodamine 101 (SR101). A swine (n = 3) model with AO was used to identify confocal features of normal brain. Images of normal brain, obvious tumor, and peritumoral zones were collected using the handheld confocal endomicroscope. Histological samples were acquired through biopsies from matched imaging areas. Samples were visualized with a benchtop confocal microscope. Histopathological features in corresponding confocal images and photomicrographs of H & E–stained tissues were reviewed.

Results

Fluorescence induced by FNa, 5-ALA, AO, AF, CV, and SR101 and detected with the confocal endomicroscope allowed interpretation of histological features. Confocal endomicroscopy revealed satellite tumor cells within peritumoral tissue, a definitive tumor border, and striking fluorescent cellular and subcellular structures. Fluorescence in various tumor regions correlated with standard histology and known tissue architecture. Characteristic features of different areas of normal brain were identified as well.

Conclusions

Confocal endomicroscopy provided rapid histological information precisely related to the site of microscopic imaging with imaging characteristics of cells related to the unique labeling features of the fluorophores. Although experimental with further clinical trial validation required, these data suggest that intraoperative confocal imaging can help to distinguish normal brain from tumor and tumor margin and may have application in improving intraoperative decisions during resection of brain tumors.